ArticleOncogene2012
Non-canonical HIF-2α function drives autonomous breast cancer cell growth via an AREG-EGFR/ErbB4 autocrine loop.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Combination therapy in combating cancer.Oncotarget · 2017Pooled it
- Transcriptome analysis of goat adipose tissue-derived mesenchymal stem cells cultured in variable oxygen conditions.Frontiers in cell and developmental biology · 2026Article
- Inherent single-cell heterogeneity of the transcriptional response to hypoxia in cancer cells.NAR cancer · 2025Article
- The DEAD-box RNA helicase DDX28 suppresses cell migration and 3D growth and invasion in MDA-MB-231 cells by altering bioenergetics.Molecular biology of the cell · 2025Article
- Spatial transcriptomic analysis of tumour with high and low CAIX expression in TNBC tissue samples using GeoMx™ RNA assay.Histology and histopathology · 2024Article
- Oxomer- and Reporter Gene-Based Analysis of FIH Activity in Cells.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Identification of an individualized therapy prognostic signature for head and neck squamous cell carcinoma.BMC genomics · 2023Article
- Differential response of luminal and basal breast cancer cells to acute and chronic hypoxia.Breast cancer research and treatment · 2023Article
- Acute vs. chronic vs. intermittent hypoxia in breast Cancer: a review on its application in in vitro research.Molecular biology reports · 2022Review
- Hypoxia and ERα Transcriptional Crosstalk Is Associated with Endocrine Resistance in Breast Cancer.Cancers · 2022Article
- The Hypoxia-Adenosine Link during Myocardial Ischemia-Reperfusion Injury.Biomedicines · 2022Review
- Neurogenic and pericytic plasticity of conditionally immortalized cells derived from renal erythropoietin-producing cells.Journal of cellular physiology · 2022Article
- Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment.Cancers · 2022Review
- Article
- eNEMAL, an enhancer RNA transcribed from a distal MALAT1 enhancer, promotes NEAT1 long isoform expression.PloS one · 2021Article
- Absence of HTATIP2 Expression in A549 Lung Adenocarcinoma Cells Promotes Tumor Plasticity in Response to Hypoxic Stress.Cancers · 2020Article
- Transcription-independent Induction of ERBB1 through Hypoxia-inducible Factor 2A Provides Cardioprotection during Ischemia and Reperfusion.Anesthesiology · 2020Article
- The role of myoglobin in epithelial cancers: Insights from transcriptomics.International journal of molecular medicine · 2020Article
- Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression.Biomolecules · 2019Review
- Hypoxia induces cancer cell-specific chromatin interactions and increases MALAT1 expression in breast cancer cells.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor progression is intrinsically tied to the clonal selection of tumor cells with acquired phenotypes allowing to cope with a hostile microenvironment. Hypoxia-inducible factors (HIFs) master the transcriptional response to local tissue hypoxia, a hallmark of solid tumors. Here, we report significantly longer patient survival in breast cancer with high levels of HIF-2α. Amphiregulin (AREG) and WNT1-inducible signaling pathway protein-2 (WISP2) expression was strongly HIF-2α-dependent and their promoters were particularly responsive to HIF-2α. The endogenous AREG promoter recruited HIF-2α in the absence of a classical HIF-DNA interaction motif, revealing a novel mechanism of gene regulation. Loss of AREG expression in HIF-2α-depleted cells was accompanied by reduced activation of epidermal growth factor (EGF) receptor family members. Apparently opposing results from patient and in vitro data point to an HIF-2α-dependent auto-stimulatory tumor phenotype that, while promoting EGF signaling in cellular models, increased the survival of diagnosed and treated human patients. Our findings suggest a model where HIF-2α-mediated autocrine growth signaling in breast cancer sustains a state of cellular self-sufficiency, thereby masking unfavorable microenvironmental growth conditions, limiting adverse selection and improving therapy efficacy. Importantly, HIF-2α/AREG/WISP2-expressing tumors were associated with luminal tumor differentiation, indicative of a better response to classical treatments. Shifting the HIF-1/2α balance toward an HIF-2-dominated phenotype could thus offer a novel approach in breast cancer therapy.
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